View Program - 63rd Annual Drosophila Research Conference

Understanding the mechanisms of epithelial wound healing is a major challenge in biology and medicine. Drosophila is a great model to study wound healing and has contributed significantly to identifying how epithelial tissue repairs a wound through coordinated changes in cellular behavior (e.g., cell migration). Wound-induced epithelial cell migration is preceded by dynamic changes in cytoskeletal structures and in tissue tension. However, it is unclear how epithelial wounding immediately affects tension in nearby epithelial cells or whether changes in tension play a role in the wound response. This study aims to characterize how wounding alters the cortical tension of apical cell borders in epithelial cells and determine factors that modulate these wound-induced tension changes. We use a laser-recoil assay to measure cortical tension immediately after a wounding the Drosophila pupal notum epithelium, and controls expressing Rok-RNAi confirmed that the technique could identify cells with reduced cortical tension. We discovered that within minutes after wounding, tension was reduced in epithelial cells closer to the wound in a distance-dependent manner. Wounds were administered by a single-shot pulsed-laser ablation, which causes a cavitation bubble that damages cells around the wound. Using a different method of laser-wounding, we found that plasma membrane microtears from the laser-induced cavitation bubble were necessary for reducing cortical tension near the wound. Previously, our group identified that the G-Protein Coupled Receptor (GPCR) Methuselah-like 10 (Mthl10) is required for calcium signaling within about a minute after wounding. Our preliminary results show that knockdown of mthl10 alters tension around the wound, abolishing the distance-dependent tension reduction after single-shot pulsed-laser wounding. This suggests that Mthl10 may be a key factor that modulates wound-induced tension changes, either by preventing tension loss or restoring tension at locations distal to the wound. Further investigation on connections between epithelial tension and other established wound responses such as calcium signaling, cell fusion, and cell migration could pave the way for deeper understanding of the mechanobiology of epithelial wound healing.

Wound-induced changes in epithelial tension